In the fetal rat Leydig cell, E2 causes an up-regulation of its receptor and an induction of the regulatory mechanism (late steroidogenic lesion, 17 hydroxylase/17-20 desmolase) that is similar to that observed in the adult rat Leydig cell. The absence of this regulation in fetal life is due to a very low aromatization capacity. Our recent studies has revealed that high doses or frequent administration of LH is able to elevate aromatase activity and consequent E2-receptor-mediated action for the induction desensitization in fetal cells. Resolution of fetal Leydig cells by centrifugal elutriation have demonstrated in addition or predominant cell type with fetal characteristics, a small population of adult-like Leydig cells and the emergence of a functional adult-like population from the fetal Leydig cell induced by gonadotropin treatment. In further studies we assessed whether hormonal modulatory actions related to changes in P-45017 alpha mRNA levels could account for steroidogenic stimulation and desensitization. We have characterized, cloned and identified a partial length rat P-45017 alpha cDNA clone. The (1 Kb) rat cDNA insert, displaying high similarity with the P-45017 alpha cDNA structures from human, bovine and porcine species, containing the conserved regions and termination codon was employed to evaluate the hormonal regulation of mRNA levels in adult and cultured fetal Leydig cells. Low hCG dose showed an early increase in mRNA levels returning to control values at later times, while a higher desensitizing dose caused a marked reduction in the mRNA (24 h) and a small recovery at 48 h. Fetal rat Leydig cells treated with E2 showed a 70% decrease in P-450 mRNA levels and testosterone production followed closely the changes in mRNA. These studies suggest that desensitization of P-45017 alpha dependent enzymes in the adult desensitization and fetal Leydig cells are related to levels mRNA. In other studies has demonstrated that Leydig cells are a site of beta-endorphin synthesis in vitro and that is under control of gonadotropins. Testosterone or its metabolites may exert a negative autocrine modulation of beta-endorphin, as inhibition of steroid biosynthesis markedly increased basal and hCG-stimulated beta-endorphin output (by 100-200%). Since we have demonstrated functional beta-endorphin receptors in Sertoli cells, the beta-endorphin produced in the Leydig cell may have paracrine effects that contribute to the quiescent state of the testis from early life to sexual maturation and it could also be involved in the modulation of tubule function during adult life.